A large body of literature describes the function and fate of blood-contacting surfaces of implanted structures, including Left Ventricular Assist Devices (LVADs), Totally Artificial Hearts (TAHs), synthetic arterial grafts, heart valves, stents, indwelling catheters and filters, and plugs for septal defects and occlusion of aneurysms and appendages. Early design goals for these surfaces were to create a biocompatible structure upon which blood would not become activated or result in inflammatory, thrombotic, or immune responses. While the issue of biocompatibility has found numerous material solutions, the creation of blood-contacting surfaces that remain clean and free of tissue over time has not occurred. Early attempts to create smooth, non-activating surfaces failed, even though surface imperfections were reduced in size below ten microns, and very hydrophobic materials, such as Teflon, were employed.
The body's response to an implanted foreign object is to first coat the object with a layer of protein, then to recruit macrophages and fibroblasts that engulf the object, or cover the object in a layer of collagen. The collagen “bag” around the object is nearly acellular (with some fibroblasts), and is generally not well vascularized.
Protein coatings form on implanted prostheses in contact with blood, followed by platelet adhesion and fibrosis. This growth is often referred to as a “pseudo-intima.” Smooth muscle cells (SMCs) and endothelial cells (ECs) may grow over the base coating creating a “neo-intima.” Some researchers continue to pursue surfaces with smoothness at or below the one-micron level, with the goal of reduced or minimal protein adhesion, and subsequently resulting in an overall thinner layer of pseudo-intima. This approach has been more effective in high flow and high shear rate settings.
The pseudo-intima, without an endothelial coating, is a potentially thrombogenic surface, subject to platelet adhesion, continued fibrotic deposition, and possibly calcification. Platelet adhesion is inhibited or eliminated by a healthy layer of ECs in contact with blood. The creation or formation of a blood contacting endothelial layer, with or without an underlying layer of SMCs, is the “holy grail” of surface implant science. The ECs actively inhibit platelet adhesion, and selectively pass nutrients and cells to and from the underlying tissues.
To date, no synthetic, blood-contacting surface material has been found that heals without incident in humans. For example, LVAD surfaces have been developed that form pseudo-intima, but with no evidence of an endothelial layer. These surfaces continue to grow and shed over time, maintaining an approximately constant thickness, but also remaining thrombogenic. While perhaps dozens of small-bore vascular graft materials have been proposed and tested, the failure rate for these devices has been poor in humans, with no clear evidence of healing of the blood-contacting surface. While EC seeded grafts and TE (tissue engineering) grafts may someday succeed in demonstrating long-term patency in humans, they may never become commercially viable. Various synthetic valves have been proposed, but none has been successfully demonstrated in humans. A need therefore exists for a synthetic material that spontaneously grows a continuous EC layer in a reasonably short period of time (weeks).
Because synthetic, blood contacting, human implant surfaces have failed to heal in applications such as small diameter arterial grafts, synthetic heart valves and blood pumps, alternative approaches have been taken, including vein grafts from the patient's legs for bypass, porcine or bovine tissue for heart valves, and rigid inert surfaces for valves and blood pumps. Vein grafts and animal tissue prostheses, however, can fail over time due to calcification, thrombosis and continuing atherosclerosis. Moreover, rigid inert surfaces require the patient to take anticoagulation medication indefinitely.